MicroRNA-124 expression in the brains of rats during early cerebral ischemia and reperfusion injury is associated with cell apoptosis involving STAT3

被引:19
作者
Zhang, Wenting
Meng, Aiguo [1 ,2 ]
机构
[1] North China Univ Sci & Technol, Dept Lab Med, Affiliated Hosp, 73 South Jianshe Rd, Tangshan 06300, Hebei, Peoples R China
[2] North China Univ Sci & Technol, Sch Clin Med, 73 South Jianshe Rd, Tangshan 06300, Hebei, Peoples R China
关键词
cerebral ischemia; reperfusion; microRNA-124; apoptosis; signal transducer and activator of transcription 3; dynamic changes; GLUCOSE DEPRIVATION; JAK2/STAT3; PATHWAY; ARTERY OCCLUSION; PROTECTS; OXYGEN; MIR-124; NEUROPROTECTION; MECHANISMS; NEURONS; FAMILY;
D O I
10.3892/etm.2019.7220
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Cerebral ischemia and reperfusion injury is a cause of death and disability in adults. MicroRNA-124 possesses protective effects against apoptosis in cerebral ischemia and reperfusion. To provide insights into the diagnosis and treatment of cerebral ischemia and reperfusion injury, the dynamic changes of microRNA-124 expression during the early stage of cerebral ischemia and reperfusion injury in rats was investigated by quantitative polymerase chain reaction. To elucidate the association between the dynamic expression of microRNA-124 and apoptosis, the expression of proteins associated with apoptosis, including caspase-3, apoptosis regulator Bcl-2 (Bcl-2) and apoptosis regulator Bax (Bax) was analyzed by immunohistochemistry and western blot analyses. As signal transducer and activator of transcription 3 (STAT3) is involved in cell apoptosis and associated with Bcl-2, the protein expression of STAT3 and its active form, phosphorylated (p-)STAT3, were analyzed by western blot analysis. The expression of microRNA-124 increased and the maximum value appeared 12 h after reperfusion. Similarly, the expression of Bcl-2 also peaked 12 h after reperfusion, however the expression of caspase-3 and Bax continued to increase after the 12 h time point. These results indicate that the expression of microRNA-124 is closely associated with Bcl-2 and serves a protective role, inhibiting apoptosis. As the upstream regulator of Bcl-2, the expression of p-STAT3 was in accordance with Bcl-2 expression and peaked 12 h after reperfusion. By contrast, STAT3 was downregulated and the minimum level of STAT3 protein was reached 12 h after reperfusion. In summary, during the early stage of cerebral ischemia and reperfusion, the dynamic expression of microRNA-124 exhibited protective effects through the inhibition of apoptosis via anti-apoptotic proteins Bcl-2 and STAT3. Conversely, caspase-3 and Bax maintain apoptosis. The present study provides evidence to aid in the understanding of cerebral ischemia and reperfusion injury and develops methods of diagnosis and therapy of this condition.
引用
收藏
页码:2870 / 2876
页数:7
相关论文
共 31 条
  • [1] RAT MIDDLE CEREBRAL-ARTERY OCCLUSION - EVALUATION OF THE MODEL AND DEVELOPMENT OF A NEUROLOGIC EXAMINATION
    BEDERSON, JB
    PITTS, LH
    TSUJI, M
    NISHIMURA, MC
    DAVIS, RL
    BARTKOWSKI, H
    [J]. STROKE, 1986, 17 (03) : 472 - 476
  • [2] MicroRNA-124 protects against focal cerebral ischemia via mechanisms involving Usp14-dependent REST degradation
    Doeppner, Thorsten R.
    Doehring, Maria
    Bretschneider, Eva
    Zechariah, Anil
    Kaltwasser, Britta
    Mueller, Barbara
    Koch, Jan C.
    Baehr, Mathias
    Hermann, Dirk M.
    Michel, Uwe
    [J]. ACTA NEUROPATHOLOGICA, 2013, 126 (02) : 251 - 265
  • [3] Improving outcome after stroke: Overcoming the translational roadblock
    Endres, Matthias
    Engelhardt, Britta
    Koistinaho, Jari
    Lindvall, Olle
    Meairs, Stephen
    Mohr, Jay P.
    Planas, Anna
    Rothwell, Nancy
    Schwaninger, Markus
    Schwab, Martin E.
    Vivien, Denis
    Wieloch, Tadeusz
    Dirnagl, Ulrich
    [J]. CEREBROVASCULAR DISEASES, 2008, 25 (03) : 268 - 278
  • [4] microRNA: Emerging therapeutic targets in acute ischemic diseases
    Fasanaro, Pasquale
    Greco, Simona
    Ivan, Mircea
    Capogrossi, Maurizio C.
    Martelli, Fabio
    [J]. PHARMACOLOGY & THERAPEUTICS, 2010, 125 (01) : 92 - 104
  • [5] The cost of cerebral ischaemia
    Flynn, R. W. V.
    MaWalter, R. S. M.
    Doney, A. S. F.
    [J]. NEUROPHARMACOLOGY, 2008, 55 (03) : 250 - 256
  • [6] MicroRNAs Regulate Mitochondrial Function in Cerebral Ischemia-Reperfusion Injury
    Hu, Yue
    Deng, Hao
    Xu, Shixin
    Zhang, Junping
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2015, 16 (10) : 24895 - 24917
  • [7] IMM-H004, a novel courmarin derivative, protects against oxygen-and glucose-deprivation/restoration-induced apoptosis in PC12 cells
    Ji, Hai-jie
    Wang, Dong-mei
    Hu, Jin-feng
    Sun, Ming-na
    Li, Gang
    Li, Zhi-peng
    Wu, Dong-hui
    Liu, Gang
    Chen, Nai-hong
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2014, 723 : 259 - 266
  • [8] Anemonin Alleviates Nerve Injury After Cerebral Ischemia and Reperfusion (I/R) in Rats by Improving Antioxidant Activities and Inhibiting Apoptosis Pathway
    Jia, Dong
    Han, Bin
    Yang, Shaowei
    Zhao, Junying
    [J]. JOURNAL OF MOLECULAR NEUROSCIENCE, 2014, 53 (02) : 271 - 279
  • [9] The RS504393 Influences the Level of Nociceptive Factors and Enhances Opioid Analgesic Potency in Neuropathic Rats
    Kwiatkowski, Klaudia
    Piotrowska, Anna
    Rojewska, Ewelina
    Makuch, Wioletta
    Mika, Joanna
    [J]. JOURNAL OF NEUROIMMUNE PHARMACOLOGY, 2017, 12 (03) : 402 - 419
  • [10] Reperfusion accelerates acute neuronal death induced by simulated ischemia
    Li, Dongdong
    Shao, Zuohui
    Vanden Hoek, Terry L.
    Brorson, James R.
    [J]. EXPERIMENTAL NEUROLOGY, 2007, 206 (02) : 280 - 287